Optimizing asthma management: Role of long-acting muscarinic antagonists
Authors: Thomas B. Casale, Michael B. Foggs, Ronald C. Balkissoon
Journal: Journal of Allergy and Clinical Immunology (2022)

Patients with asthma who are suboptimally responsive to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) are frequently exposed to oral corticosteroids and high-dose ICS, which can lead to significant side effects. Long-acting muscarinic antagonists (LAMAs) have demonstrated efficacy and safety in a subset of these patients. This review summarizes the results of key studies using LAMAs in patients with asthma aged 12 years or older. LAMA as an add-on treatment improved lung function and asthma control in patients with uncontrolled asthma across studies. The efficacy of LAMAs as an add-on to ICS was superior to that of placebo and ICS dose escalation and comparable with that of LABAs. LAMA plus ICS plus LABA provided modest improvements in bronchodilation and increased the time to first severe exacerbation versus ICS plus LABA. Single-inhaler triple therapy was associated with decreased health care resource utilization and improved cost-effectiveness versus multiple inhalers. LAMAs were generally well tolerated; asthma exacerbations, bronchitis, and nasopharyngitis were common adverse events with LAMA in combination with ICS alone or ICS plus LABA. Thus, the overall evidence presented in this review supports the use of add-on LAMA treatment as a reasonable option in patients with asthma uncontrolled with ICS plus LABA or ICS alone. Patients with asthma who are suboptimally responsive to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) are frequently exposed to oral corticosteroids and high-dose ICS, which can lead to significant side effects. Long-acting muscarinic antagonists (LAMAs) have demonstrated efficacy and safety in a subset of these patients. This review summarizes the results of key studies using LAMAs in patients with asthma aged 12 years or older. LAMA as an add-on treatment improved lung function and asthma control in patients with uncontrolled asthma across studies. The efficacy of LAMAs as an add-on to ICS was superior to that of placebo and ICS dose escalation and comparable with that of LABAs. LAMA plus ICS plus LABA provided modest improvements in bronchodilation and increased the time to first severe exacerbation versus ICS plus LABA. Single-inhaler triple therapy was associated with decreased health care resource utilization and improved cost-effectiveness versus multiple inhalers. LAMAs were generally well tolerated; asthma exacerbations, bronchitis, and nasopharyngitis were common adverse events with LAMA in combination with ICS alone or ICS plus LABA. Thus, the overall evidence presented in this review supports the use of add-on LAMA treatment as a reasonable option in patients with asthma uncontrolled with ICS plus LABA or ICS alone. 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For a complete summary of studies reviewed in the preparation of this article, please see this article's Online Repository at www.jacionline.org.Table IWeighting of studies comparing LAMA with other treatments in adults or adolescents with asthmaAuthors (trial name, if any)Previous treatmentLAMA-containing intervention arm (n)Comparator(s) (n)Systematic reviewsSobieraj et al,34Sobieraj D.M. Baker W.L. Nguyen E. Weeda E.R. Coleman C.I. White C.M. et al.Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis.JAMA. 2018; 319: 1473-1484Crossref PubMed Scopus (60) Google Scholar 2018ICSICS plus LAMA;15 RCTs in patients with uncontrolled persistent asthma (n = 7122)Pbo∗LAMA/comparator was used as an add-on to previous treatment.Kew et al,35Kew K.M. Evans D.J. Allison D.E. Boyter A.C. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus addition of long-acting beta2-agonists (LABA) for adults with asthma.Cochrane Database Syst Rev. 2015; 2015: CD011438Google Scholar 2015ICSICS plus LAMA; 8 studies including 4 double-blind, double-dummy studies (≈n = 2000)LABA∗LAMA/comparator was used as an add-on to previous treatment.Kew and Dahri,36Kew K.M. Dahri K. Long-acting muscarinic antagonists (LAMA) added to combination lo